BACKGROUND: A specific type of dietary polyunsaturated fat - omega-3 fatty acids (w-3 FAs) - has been found to be protective of death from cardiovascular disease. There are two general sources of these dietary w-3 FAs: marine sources provide EPA and DHA, and plant food sources provide ALA. These are also widely available as nutritional supplements. Whether one form or the other is more effective in disease prevention remains controversial. Part of the controversy is due to the lack of consensus on optimal doses from the different sources and/or to the different types of people studied. Potential benefits are likely to be increased for those with insulin resistance (the metabolic syndrome) who have elevated levels of both triglycerides and inflammatory markers. LONG TERM OBJECTIVE is to contrast different doses and sources of w-3 FA's for their potential effects on inflammatory markers and related health measures. SPECIFIC AIMS: The first aim is to contrast the marine type w-3 FAs to the plant-based w-3 FAs (EPA + DHA vs. ALA). The second aim is to contrast two doses of each of these types of w-3 FAs. The lower dose has been selected to be reflective of what would be considered a high but realistic dose to obtain strictly from food sources. The higher dose will be 3 times the lower dose and would likely only be realistically achievable if dietary supplements were consumed in addition to food sources. DESIGN: A randomized clinical trial will be employed in this study. One hundred adults found to have the "metabolic syndrome", who are at increased risk of heart disease, will be randomly assigned to either a placebo group, or to take one of four w-3 FA regimens for eight weeks: Low EPA/DHA, High EPA/DHA, Low ALA or High ALA (i.e. 20 per group). Blood samples will be collected at multiple time points (0, 2, 4 and 8 weeks) to examine the effect of the duration of supplement intake on study outcomes. The primary study outcomes are CRP, IL-6, TNF- alpha, and slCAM-1. SIGNIFICANCE: This generally safe and relatively inexpensive dietary approach to heart disease prevention and treatment has considerable potential, but more information is needed regarding optimal doses and sources of w-3 FAs, as well as what particular markers of inflammation may be involved in its effects. The adults with the metabolic syndrome selected for this study are those that are at increased risk of heart disease, and those most likely to be benefit from the different therapies tested. [unreadable] [unreadable] [unreadable]